tbuckley/cabot-search huggingface dataset:
Adverse childhood experiences and mental health problems in a nationally representative study of heterosexual, homosexual and bisexual Danes
Authors: Josefine Bernhard Andresen, Christian Graugaard, Mikael Andersson, Mikkel Kjær Bahnsen, Morten Frisch
Journal: World Psychiatry (2022)

Non-heterosexual persons more often report adverse childhood experiences (ACEs) than heterosexuals, and they generally bear a greater burden of mental health challenges. However, population-based data on this topic are scarce. In a nationally representative study within the Project SEXUS, one of the world's largest cohort studies on sexual health, we used data from 57,479 individuals in Denmark to explore the interplay between ACEs and mental health problems among self-identified heterosexual, homosexual and bisexual persons, and among self-identified heterosexuals with or without same-sex sexual experience. Compared to heterosexuals, non-heterosexual persons were more likely to report most of the studied ACEs, with odds ratios (ORs) for the ACE category "abuse" ranging from 1.38 to 1.75 for homosexual women, from 1.76 to 2.65 for homosexual men, from 2.52 to 3.64 for bisexual women, and from 1.58 to 6.07 for bisexual men. Furthermore, non-heterosexual persons had consistently and statistically significantly higher odds for mental health problems (ORs: 1.50 to 4.63). Combinations of ACEs with a non-heterosexual identity resulted in markedly elevated odds for mental health problems, particularly among bisexual individuals. This included high odds for suicidal thoughts/attempts among bisexual persons with a history of "neglect" (women: OR=12.82; men: OR=35.24) and "abuse" (women: OR=11.81; men: OR=11.65). Among self-identified heterosexuals, combinations of ACEs with same-sex sexual experience were associated with consistently elevated odds for mental health problems (ORs: 2.22 to 12.04). The greater burden of ACEs among self-identified homosexuals and, most notably, bisexuals may account for part of their excess risk of mental health problems. These findings emphasize the public health importance of preventive measures to minimize the burden of ACEs and avert their harmful long-term effects. Moreover, they highlight the need to safeguard the welfare of children and adolescents with non-conforming expressions of sexuality.
Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury
Authors: Tim Stüdemann, Judith Rössinger, Christoph Manthey, Birgit Geertz, Rajiven Srikantharajah, Constantin von Bibra, Aya Shibamiya, Maria Köhne, Antonius Wiehler, J. Simon Wiegert, Thomas Eschenhagen, Florian Weinberger
Journal: Circulation (2022)

Background: Transplantation of pluripotent stem cell–derived cardiomyocytes represents a promising therapeutic strategy for cardiac regeneration, and the first clinical studies in patients with heart failure have commenced. Yet, little is known about the mechanism of action underlying graft-induced benefits. Here, we explored whether transplanted cardiomyocytes actively contribute to heart function. Methods: We injected cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model. Results: Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function in ≈50% (7/13) animals that was fully reversible with the offset of photostimulation. Conclusions: Our optogenetic approach demonstrates that transplanted cardiomyocytes can actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.
ATIC-Associated De Novo Purine Synthesis Is Critically Involved in Proliferative Arterial Disease
Authors: Qian Ma, Qiuhua Yang, Jiean Xu, Xiaoyu Zhang, David Kim, Zhiping Liu, Qingen Da, Xiaoxiao Mao, Yaqi Zhou, Yongfeng Cai, Vidhi Pareek, Ha Won Kim, Guangyu Wu, Zheng Dong, Wen-Liang Song, Lin Gan, Chunxiang Zhang, Mei Hong, Stephen J. Benkovic, Neal L. Weintraub, David Fulton, John M. Asara, Issam Ben-Sahra, Yuqing Huo
Journal: Circulation (2022)

Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of arterial diseases, especially in arterial restenosis after angioplasty or stent placement. VSMCs reprogram their metabolism to meet the increased requirements of lipids, proteins, and nucleotides for their proliferation. De novo purine synthesis is one of critical pathways for nucleotide synthesis. However, its role in proliferation of VSMCs in these arterial diseases has not been defined.
Deleterious Mutations and the Rare Allele Burden on Rice Gene Expression
Authors: Zoe Lye, Jae Young Choi, Michael D Purugganan
Journal: Molecular Biology and Evolution (2022)

Abstract Deleterious genetic variation is maintained in populations at low frequencies. Under a model of stabilizing selection, rare (and presumably deleterious) genetic variants are associated with increase or decrease in gene expression from some intermediate optimum. We investigate this phenomenon in a population of largely Oryza sativa ssp. indica rice landraces under normal unstressed wet and stressful drought field conditions. We include single nucleotide polymorphisms, insertion/deletion mutations, and structural variants in our analysis and find a stronger association between rare variants and gene expression outliers under the stress condition. We also show an association of the strength of this rare variant effect with linkage, gene expression levels, network connectivity, local recombination rate, and fitness consequence scores, consistent with the stabilizing selection model of gene expression.
Genomic Landscapes and Hallmarks of Mutant RAS in Human Cancers
Authors: Robert B. Scharpf, Archana Balan, Biagio Ricciuti, Jacob Fiksel, Christopher Cherry, Chenguang Wang, Michele L. Lenoue-Newton, Hira A. Rizvi, James R. White, Alexander S. Baras, Jordan Anaya, Blair V. Landon, Marta Majcherska-Agrawal, Paola Ghanem, Jocelyn Lee, Leon Raskin, Andrew S. Park, Huakang Tu, Hil Hsu, Kathryn C. Arbour, Mark M. Awad, Gregory J. Riely, Christine M. Lovly, Valsamo Anagnostou
Journal: Cancer Research (2022)

The RAS family of small GTPases represents the most commonly activated oncogenes in human cancers. To better understand the prevalence of somatic RAS mutations and the compendium of genes that are coaltered in RAS-mutant tumors, we analyzed targeted next-generation sequencing data of 607,863 mutations from 66,372 tumors in 51 cancer types in the AACR Project GENIE Registry. Bayesian hierarchical models were implemented to estimate the cancer-specific prevalence of RAS and non-RAS somatic mutations, to evaluate co-occurrence and mutual exclusivity, and to model the effects of tumor mutation burden and mutational signatures on comutation patterns. These analyses revealed differential RAS prevalence and comutations with non-RAS genes in a cancer lineage-dependent and context-dependent manner, with differences across age, sex, and ethnic groups. Allele-specific RAS co-mutational patterns included an enrichment in NTRK3 and chromatin-regulating gene mutations in KRAS G12C-mutant non-small cell lung cancer. Integrated multiomic analyses of 10,217 tumors from The Cancer Genome Atlas (TCGA) revealed distinct genotype-driven gene expression programs pointing to differential recruitment of cancer hallmarks as well as phenotypic differences and immune surveillance states in the tumor microenvironment of RAS-mutant tumors. The distinct genomic tracks discovered in RAS-mutant tumors reflected differential clinical outcomes in TCGA cohort and in an independent cohort of patients with KRAS G12C-mutant non-small cell lung cancer that received immunotherapy-containing regimens. The RAS genetic architecture points to cancer lineage-specific therapeutic vulnerabilities that can be leveraged for rationally combining RAS-mutant allele-directed therapies with targeted therapies and immunotherapy.
Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post‐hoc analysis from the REWIND randomized trial
Authors: Kelley R.H. Branch, Gilles R. Dagenais, Alvaro Avezum, Jan Basile, Ignacio Conget, William C. Cushman, Petr Jansky, Mark Lakshmanan, Fernando Lanas, Lawrence A. Leiter, Prem Pais, Nana Pogosova, Peter J. Raubenheimer, Lars Ryden, Jonathan E. Shaw, Wayne H.H. Sheu, Theodora Temelkova‐Kurktschiev, M. Angelyn Bethel, Hertzel C. Gerstein, Ramasundarahettige Chinthanie, Jeffrey L. Probstfield
Journal: European Journal of Heart Failure (2022)
Battle of the γδ T cell subsets in the gut
Authors: Sofia Mensurado, Bruno Silva-Santos
Journal: Trends in cancer (2022)

In a study in Science, Reis et al. describe a temporal segregation of γδ T cell activities in colorectal cancer (CRC). Initially tumor surveillance is orchestrated by interferon-γ (IFN-γ)-producing and cytotoxic γδ T cell subsets, but once the tumor thrives, it becomes infiltrated by interleukin (IL)-17+ γδ T cell subsets that promote its growth.
S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission
Authors: Linlu Tian, Yongxia Wu, Hee-Jin Choi, Xiaohui Sui, Xinlei Li, M. Hanief Sofi, Mohamed Faisal Kassir, Xiao Chen, Shikhar Mehrotra, Besim Ogretmen, Xue-Zhong Yu
Journal: Cellular and Molecular Immunology (2022)
Drinking Water–Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study
Authors: Emma M. Rosen, Nadine Kotlarz, Detlef R.U. Knappe, C. Suzanne Lea, David N. Collier, David B. Richardson, Jane A. Hoppin
Journal: Environmental Health Perspectives (2022)

Background: Residents of Wilmington, North, Carolina, were exposed to drinking water contaminated by fluoroethers and legacy per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with fluoroether exposure occurring from 1980 to 2017. PFOA and PFOS have previously been associated with metabolic dysfunction; however, few prior studies have examined associations between other PFAS and lipid levels. Objectives: We measured the association between serum fluoroether and legacy PFAS levels and various cholesterol outcomes. Methods: Participants in the GenX Exposure Study contributed nonfasting blood samples in November 2017 and May 2018 that were analyzed for 20 PFAS (10 legacy, 10 fluoroethers) and serum lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] and calculated non-HDL cholesterol. We estimated covariate-adjusted associations between quartiles of exposure to each of the PFAS measures (as well as the summed concentrations of legacy PFAS, fluoroethers, and all 10 targeted PFAS) and lipid outcomes by fitting inverse probability of treatment weighted linear regressions. Results: In this cross-sectional study of 326 participants (age range 6–86 y), eight PFAS were detected in >50% of the population. For PFOS and perfluorononanoic acid (PFNA), non-HDL cholesterol was approximately 5mg/dL higher per exposure quartile increase: [PFOS: 4.89; 95% confidence interval (CI): 0.10, 9.68 and PFNA: 5.25 (95% CI: 0.39, 10.1)], whereas total cholesterol was approximately 6mg/dL higher per quartile [PFOS: 5.71 (95% CI: 0.38, 11.0), PFNA: 5.92 (95% CI: 0.19, 11.7)]. In age-stratified analyses, associations were strongest among the oldest participants. Two fluoroethers were associated with higher HDL, whereas other fluoroether compounds were not associated with serum lipid levels. Discussion: PFNA and PFOS were associated with higher levels of total and non-HDL cholesterol, with associations larger in magnitude among older adults. In the presence of these legacy PFAS, fluoroethers appeared to be associated with HDL but not non-HDL lipid measures. https://doi.org/10.1289/EHP11033
National Cancer Institute–Funded Social Risk Research in Cancer Care Delivery: Opportunities for Future Research
Authors: Janeth I Sanchez, Brenda A Adjei, Gurvaneet Randhawa, Josh Medel, Michelle Doose, April Oh, Paul B Jacobsen
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Cancer patients and survivors with food insecurity, housing instability, and transportation-related barriers face challenges in access and utilization of quality cancer care thereby adversely impacting their health outcomes. This portfolio analysis synthesized and described National Cancer Institute (NCI)–supported social risk research focused on assessing food insecurity, housing instability, and transportation-related barriers among individuals diagnosed with cancer. Methods We conducted a query using the National Institutes of Health iSearch tool to identify NCI-awarded extramural research and training grants (2010-2022). Grant abstracts, specific aims, and research strategies were coded for research characteristics, study population, and outcomes. Results Of the 30 grants included in this analysis, most assessed transportation-related barriers as patient-level social needs. Grants focused on community-level social risks, food insecurity, and housing instability were largely absent. Most grants included activities that identified the presence of social risks and/or needs (n = 24), connected patients to social care resources (n = 10), and engaged community members or organizations to inform the research study (n = 9). Of the grants, 18 focused on a single type of cancer, primarily breast cancer, and more than half focused on the treatment and survivorship phases. Conclusions In the last decade, there has been limited NCI-funded social risk research grants focused on food insecurity and housing instability. Findings highlight opportunities for future cancer care delivery research, including community and health system–level approaches that integrate social and clinical care to address social risks and social needs. Such efforts can help improve outcomes of populations that experience cancer health and health-care disparities.
Detection of a Highly Divergent Type 3 Vaccine-Derived Poliovirus in a Child with a Severe Primary Immunodeficiency Disorder — Chongqing, China, 2022
Authors: Ning Yao, Yang Liu, Jia-Wei Xu, Qing Wang, Zun-Dong Yin, Ning Wen, Hong Yang, Lance E. Rodewald, Zhi-Yong Zhang
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Oral poliovirus vaccine (OPV) has proven to be highly effective in the global effort to eradicate poliomyelitis because of its ability to induce both humoral and intestinal immunity, ease of administration, and low cost (1). Sabin-strain OPV contains live attenuated virus and induces immunity by replicating in the intestinal tract, triggering an immune response that clears the vaccine virus. However, among undervaccinated communities and persons with immunodeficiency, OPV mutations that arise during prolonged replication can result in the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs). In addition, OPV has resulted in rare cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccine recipients or their close contacts (1). Identification of circulating polioviruses relies on surveillance of acute flaccid paralysis (AFP) and environmental surveillance of wastewater (i.e., sewage). In 2022, type 3 VDPV (VDPV3) was detected in stool specimens from an infant with primary immunodeficiency disorder (PID) through a pilot surveillance program to identify VDPVs in children with PIDs. Integrated AFP, environmental, and immunodeficiency-associated VDPV (iVDPV) surveillance is critical to detecting and containing all polioviruses and achieving the goal of global polio eradication.
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis
Authors: Yuhe Huang, Weiqi Hong, Xiawei Wei
Journal: Journal of Hematology & Oncology (2022)

Abstract Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT is associated with malignant properties of tumor cells during cancer progression and metastasis, including promoted migration and invasiveness, increased tumor stemness, and enhanced resistance to chemotherapy and immunotherapy. EMT is tightly regulated by a complex network which is orchestrated with several intrinsic and extrinsic factors, including multiple transcription factors, post-translational control, epigenetic modifications, and noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, and the stages of tumorigenesis involved in the EMT process and discussed the dynamic non-binary process of EMT and its role in tumor metastasis. Finally, we summarized the challenges of chemotherapy and immunotherapy in EMT and proposed strategies for tumor therapy targeting EMT.
Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987
Authors: Ulla Lång, Hugh Ramsay, Kathryn Yates, Juha Veijola, David Gyllenberg, Mary C. Clarke, Finbarr P. Leacy, Mika Gissler, Ian Kelleher
Journal: World Psychiatry (2022)

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2-8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9-14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13-17 years) (OR=24.2, 95% CI: 21.2-27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7-1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6-3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2-2.5). Of all psychosis/bipolar diagnoses by age 28 years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high-risk but also a high-capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large-scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.
Semen Quality Following Long-term Occupational Exposure to Formaldehyde in China
Authors: Mo-qi Lv, Hai-xu Wang, Yan-qi Yang, Rui-fang Sun, Pan Ge, Jian Zhang, Wen-bao Zhao, Shui-ping Han, Dang-xia Zhou
Journal: JAMA Network Open (2022)

Importance The potential effects of long-term occupational exposure to formaldehyde (FA) on human semen quality is not clear. Objective To assess whether long-term occupational exposure to FA is associated with semen quality. Design, Setting, and Participants This population-based cohort study was conducted from June 1 to June 30, 2021, in Xi’an, China. Participants were adults aged 23 to 40 years who had lived in the study area for 24 months or longer. Data analysis was performed from September 1 to October 1, 2021. Exposures Long-term occupational exposure to FA was measured using a formaldehyde detector, and the FA exposure index (FEI) was calculated as follows: FEI = final concentration of FA (mg/m 3 ) × work time during a workday (hour) × cumulative workdays (year). Main Outcomes and Measures Semen samples were collected by masturbation after 3 to 7 days of abstinence and were then assessed by the computer-automated semen analysis system, Baso-Papanicolaou staining, and sperm-chromatin structure assay. Results A total of 205 men (mean [SD] age, 29.49 [3.64] years), with 124 individuals in the FA exposure group (mean [SD] FEI, 73.72 [54.86]) and 81 age-matched controls, were included in the final analysis. Long-term personal occupational exposure to FA was significantly associated with poor semen quality. Specifically, a 1-unit increase in FEI was associated with a change of −0.99% (95% CI, −1.00% to −0.98%) in total sperm motility, −0.99% (95% CI, −0.99% to −0.97%) in progressive sperm motility, −0.05% (95% CI, −0.08% to −0.02%) in curvilinear velocity, −0.07% (95% CI, −0.10% to −0.04%) in straight line velocity, −0.07% (95% CI, −0.10% to −0.04%) in time-average velocity, −0.98% (95% CI, −0.99% to −0.93%) in normal sperm morphology, −0.24% (95% CI, −0.35% to −0.11%) in seminal neutral glucosidase, −0.61% (95% CI, −0.66% to −0.56%) in seminal plasma zinc, 0.52% (95% CI, 0.15% to 1.02%) in beat cross frequency, and 0.10% (95% CI, 0.06% to 0.14%) in the DNA fragmentation index. These associations remained significant after adjusting for confounding factors. Furthermore, subgroup analysis found that high levels of oxidative stress might promote the associations between FA exposure and semen quality. Conclusions and Relevance This study found an association between long-term occupational exposure to FA and semen quality. This deterioration was dose and time dependent and might be induced by oxidative stress.
Wastewater surveillance of pathogens can inform public health responses
Authors: Megan B. Diamond, Aparna Keshaviah, Ana I. Bento, Otakuye Conroy-Ben, Erin M. Driver, Katherine B. Ensor, Rolf U. Halden, Loren P. Hopkins, Katrin G. Kuhn, Christine L. Moe, Eric C. Rouchka, Ted Smith, Bradley S. Stevenson, Zachary Susswein, Jason R. Vogel, Marlene K. Wolfe, Lauren B. Stadler, Samuel V. Scarpino
Journal: Nature Medicine (2022)
Quantum dots: The cutting-edge nanotheranostics in brain cancer management
Authors: Pratik Chakraborty, Sabya Sachi Das, Abhijit Dey, Apala Chakraborty, Chiranjib Bhattacharyya, Ramesh Kandimalla, Biswajit Mukherjee, Abilash Valsala Gopalakrishnan, Sandeep Kumar Singh, Shubham Kant, Parma Nand, Shreesh Ojha, Pravir Kumar, Niraj Kumar Jha, Saurabh Kumar Jha, Saikat Dewanjee
Journal: Journal of Controlled Release (2022)
No differences in myocardial perfusion between treatment‐naive, early rheumatoid arthritis patients and healthy controls
Authors: John D. Biglands, Bara Erhayiem, Graham Fent, John P. Greenwood, Raluca B. Dumitru, Jacqueline Andrews, Paul Emery, Maya H. Buch, Sven Plein
Journal: Arthritis & Rheumatology (2022)

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